Integrated studies on embryonic survival and prenatal development in swine

作为“表型可塑性”的一个重要经济方面，猪出生后生长表现的可变性的产前编程。牲畜物种的终生生产潜力最终由动物的高度选择的基因和环境之间的相互作用所控制。这些环境因素在出生前和出生后都起作用。越来越清楚的是，一生的增长潜力可能会受到发生在胚胎和胎儿发育早期的关键事件的限制。早期胚胎发育的编程是一个复杂的过程，最初由受精卵母细胞胞浆中的母源调节因子控制，然后受独特重组的胚胎基因组的表达控制。然而，胚胎基因组的表达受到表观遗传(环境)调控，由仅来自母亲或父亲的等位基因表达的“印记”基因介导。基因印记的机制涉及DNA甲基化，有证据表明，这一过程可以通过母亲的营养来改变。“印记基因”在调节胎盘发育、胎儿对母体营养的需求以及由此导致的胎儿宫内生长迟缓(IUGR)方面的明确作用尚未在猪身上得到证实。我们NSERC资助的研究的一个主要目标是确定基因印记作为这些表观遗传效应的中介参与其中。最先进的应用基因组技术(基因大阵列和候选基因微阵列分析)将被用来在比较动物发育生物学的更广泛的背景下研究不同的营养方案和哺乳分解代谢、功能营养和无意的宫内拥挤对早期胚胎存活和出生前规划的影响。在像猪这样重要的肉类生产物种的背景下，肌肉分化(肌肉发生)的调节将是一个特别关注的问题，因为它是限制出生后生长性能的一个因素。

Prenatal programming of variability in postnatal growth performance in swine as an economically important aspect of "phenotypic plasticity". Lifetime production potential in livestock species is ultimately controlled by the interaction between the highly selected genotype of an animal and its environment. These environmental factors are operative in both the prenatal and postnatal periods. It is becoming clear that lifetime growth potential may be limited by key events occurring early in embryonic and fetal development. Programming of early embryonic development is a complex process that is initially controlled by maternally derived regulators in the cytoplasm of the fertilized oocyte, and is then controlled by the expression of the uniquely reconstituted embryonic genome. However, expression of the embryonic genome is subject to epigenetic (environmental) regulation, mediated by "imprinted" genes that are only expressed from either the maternal or the paternal allele. The mechanism of gene imprinting involves DNA methylation, and there is evidence that this process can be altered by maternal nutrition. An unequivocal role of "imprinted genes" in the regulation of placental development, fetal demand for maternal nutrients and resulting fetal intrauterine growth retardation (IUGR), has not been established in the pig. A primary objective of our NSERC-funded research is to determine the involvement of gene imprinting as a mediator of these epigenetic effects. State-of-the-art applied genomic techniques (gene macro-arrays and candidate gene micro-array analyses) will be used to study effects of different nutritional regimens and lactational catabolism, functional nutrients, and inadvertent intra-uterine crowding on early embryonic survival and pre-natal programming in the broader context of comparative animal developmental biology. In the context of an important meat producing species like the pig, the regulation of muscle differentiation (myogenesis) will be a particular focus, as a factor limiting postnatal growth performance.